Analyzing the number of common integration sites of viral vectors - new methods and computer programs

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Ulrich Abel - , Universität Heidelberg, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Annette Deichmann - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Ali Nowrouzi - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Richard Gabriel - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Cynthia C. Bartholomae - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Hanno Glimm - , Deutsches Krebsforschungszentrum, DKFZ Standort Dresden, Nationales Centrum für Tumorerkrankungen Dresden, Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Christof von Kalle - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Manfred Schmidt - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)

Abstract

Vectors based on γ-retroviruses or lentiviruses have been shown to stably express therapeutical transgenes and effectively cure different hematological diseases. Molecular follow up of the insertional repertoire of gene corrected cells in patients and preclinical animal models revealed different integration preferences in the host genome including clusters of integrations in small genomic areas (CIS; common integrations sites). In the majority, these CIS were found in or near genes, with the potential to influence the clonal fate of the affected cell. To determine whether the observed degree of clustering is statistically compatible with an assumed standard model of spatial distribution of integrants, we have developed various methods and computer programs for γ-retroviral and lentiviral integration site distribution. In particular, we have devised and implemented mathematical and statistical approaches for comparing two experimental samples with different numbers of integration sites with respect to the propensity to form CIS as well as for the analysis of coincidences of integration sites obtained from different blood compartments. The programs and statistical tools described here are available as workspaces in R code and allow the fast detection of excessive clustering of integration sites from any retrovirally transduced sample and thus contribute to the assessment of potential treatment-related risks in preclinical and clinical retroviral gene therapy studies.

Details

OriginalspracheEnglisch
Aufsatznummere24247
FachzeitschriftPloS one
Jahrgang6
Ausgabenummer10
PublikationsstatusVeröffentlicht - 2011
Peer-Review-StatusJa

Externe IDs

PubMed 22022353

Schlagworte

ASJC Scopus Sachgebiete